Naltrexone and Behavioral Drug and HIV Risk Reduction Counseling in Russia

描述（由申请人提供）：俄罗斯联邦估计有160万至400万阿片剂使用者（大多数使用注射药物）和94万多艾滋病毒感染者（80%与注射药物有关），面临着艾滋病毒爆炸性流行的前景。目前在俄罗斯，住院戒毒后口服纳曲酮维持（NMT）是唯一的药物治疗阿片类药物依赖。以证据为基础的咨询，以减少艾滋病毒传播和戒毒后的复发，并没有广泛提供或常规提供。NMT采用医学模式，医生只提供简短的医疗管理（MM）。包括我们的初步研究数据在内的一些考虑表明，通过使用缓释纳曲酮（XR/NTX）代替口服纳曲酮（O/NTX），以及将NMT与行为药物和艾滋病毒风险降低咨询（BDRC）相结合，可以提高NMT的疗效。通过减少依从性问题和治疗损耗，XR/NTX可以提高临床疗效（即减少复发风险、IDU和其他与药物使用相关的危险行为）。BDRC还可以改善药物依从性，促进行为改变，从而降低复发风险、IDU和其他与药物和性相关的艾滋病毒风险行为。然而，纳曲酮制剂（O/NTX vs. XR/NTX）和咨询（MM单独或联合BDRC）的各种组合在减少药物和性相关HIV风险行为和增加阿片类药物戒断持续时间方面的功效和成本效益尚未得到系统评估。因此，我们建议进行一项2x2因子随机临床试验，评估两种药物配方（O/NTX和XR/NTX）和两种手册指导的咨询条件（MM单独或MM+BDRC）的疗效和成本效益，以及药物和咨询条件之间的潜在相互作用。解毒后，阿片类药物依赖受试者（N=320）将被随机分配到四个治疗组中的一个进行6个月的治疗：O/NTX+MM、XR/NTX+MM、O/NTX+MM+BDRC或XR/NTX+MM+BDRC。[主要结果措施包括减少与性和毒品有关的艾滋病毒风险行为，[减少非法阿片类药物的使用]和保持治疗。其他成果措施包括减少阿片剂或其他药物使用频率、健康状况和保健利用、犯罪行为和逮捕，以及改善职业和家庭功能和生活质量。所有研究参与者将在6个月的治疗期和积极治疗期后的6个月内进行基线和每月评估。数据分析将重点放在意向处理样本上。研究结果将允许评估XR/NTX是否具有优于O/NTX的疗效或更具成本效益，BDRC加MM是否具有优于MM的疗效或更具成本效益，以及药物和咨询的特定组合是否具有优于其他组合的疗效或更具成本效益。

DESCRIPTION (provided by applicant): With an estimated 1.6-4 million opiate users (majority with injection drug use (IDU)) and more than 940,000 HIV infected individuals (80% linked to IDU), the Russian Federation is facing the prospect of an explosive HIV epidemic. Currently in Russia, inpatient detoxification followed by oral naltrexone maintenance (NMT) is the only pharmacologic treatment for opiate dependence. Evidence-based counseling to reduce HIV transmission and relapse following detoxification is not widely available or routinely provided. NMT is offered using a medical model, with physicians providing only brief medical management (MM). Several considerations, including data from our preliminary studies, suggest that the efficacy of NMT may be improved by using extended-release naltrexone (XR/NTX) instead of oral naltrexone (O/NTX) and by combining NMT with behavioral drug and HIV risk reduction counseling (BDRC). [By reducing adherence problems and treatment attrition, XR/NTX may improve clinical effectiveness (i.e., reduce relapse risk, IDU, and other risk behaviors associated with drug use).] BDRC may also improve medication adherence and promote behavioral change leading to reduced relapse risk, IDU, and other drug- and sex-related HIV risk behaviors. However, the efficacy and cost-effectiveness for reducing drug- and sex-related HIV risk behaviors and increasing duration of opioid abstinence of the various combinations of naltrexone formulation (O/NTX vs. XR/NTX) and counseling (MM only or combined with BDRC) have not been systematically evaluated. Consequently, we are proposing a 2x2 factorial randomized clinical trial evaluating the efficacy and cost-effectiveness of two medication formulations (O/NTX and XR/NTX) and two manual-guided counseling conditions (MM only or MM+BDRC) and the potential interactions between medications and counseling conditions. Following detoxification, opiate dependent subjects (N=320) will be randomly assigned to 6 months of treatment in one of four treatment groups: O/NTX+MM, XR/NTX+MM, O/NTX+MM+BDRC, or XR/NTX+MM+BDRC. [Primary outcome measures include reductions in sex- and drug-related HIV risk behaviors, [reductions in illicit opiate use], and treatment retention. Other outcome measures include reductions in frequency of opiate or other drug use, health status and healthcare utilization, criminal behavior and arrests, and improvements in vocational and family functioning and quality of life.] All study participants will be assessed at baseline and monthly during the 6 month treatment phase and for 6 months following the active treatment phase. Data analyses will focus on the intention-to treat sample. The study results will allow evaluation of whether XR/NTX has superior efficacy or is more cost-effective than O/NTX, whether BDRC plus MM has superior efficacy or is more cost- effective than MM only, and whether particular combinations of medications and counseling have superior efficacy or are more cost-effective than other combinations. PUBLIC HEALTH RELEVANCE: The long-term goals of this study are to foster development and dissemination of evidence-based behavioral and pharmacological treatments to reduce HIV transmission, injection drug use (IDU), and heroin use in Russia. This study will examine the effects of combining behavioral therapy with naltrexone pharmacotherapy for the treatment of opiate dependence and reduction of HIV risks in opiate dependent individuals. Specifically the study will determine whether extended-release injection naltrexone has greater efficacy and is more cost- effective than oral naltrexone maintenance, whether behavioral drug and HIV risk reduction counseling (BDRC) combined with brief, medical management (MM) has greater efficacy and is more cost-effective than MM only, and whether particular combinations of medication formulation and counseling (MM only or MM plus BDRC) have greater efficacy or are more cost-effective than other combinations.